Serum levels of P185-HER-2 were measured in 137 breast cancer patients and in 40 controls. The patients were divided into 4 groups: group A - 40 newly diagnosed patients; group B - 57 patients on long-term follow-up without active disease; group C - 26 patients with metastatic disease and group D - 5 patients with locally advanced inoperable tumors. The median level in controls was 4.8 U/l. The median P185 serum levels in groups C and D were significantly higher compared to groups A and B. In group C 60% and in group D 100% of patients had baseline elevated levels of serum P185 (>5 U/l) compared to 28% in groups A and B. Of the 14 patients in group A with elevated baseline levels of serum P185, 6 (43%) developed metastasis during the 24-month follow-up period. On serial measurements during follow-up in 23 patients of group A, 3 relapsed and the P185 level increased. In group C, serial measurements in patients with elevated baseline levels of P185 correlated with clinical response to therapy. These data suggest that serum levels of P185 are elevated in patients with metastatic disease. High initial P185 serum levels in new patients may have prognostic significance. Serial measurements of P185 in asymptomatic patients may help in monitoring disease state. In metastatic patients, serial P185 determination may be of benefit in assessing response to therapy.